Simultaneously increased expression of glucocorticoid‑induced tumor necrosis factor receptor and its ligand contributes to increased interleukin‑5/13‑producing group 2 innate lymphocytes in murine asthma

Zhang,Mengying; Wan,Jie; Xu,Yunyun; Zhang,Danyi; Peng,Jingjing; Qi,Chen; Guo,Qi; Xia,Sheng; Su,Zhaoliang; Wang,Shengjun; Xu,Huaxi

doi:10.3892/mmr.2017.6500

Simultaneously increased expression of glucocorticoid‑induced tumor necrosis factor receptor and its ligand contributes to increased interleukin‑5/13‑producing group 2 innate lymphocytes in murine asthma

Authors:
- Mengying Zhang
- Jie Wan
- Yunyun Xu
- Danyi Zhang
- Jingjing Peng
- Chen Qi
- Qi Guo
- Sheng Xia
- Zhaoliang Su
- Shengjun Wang
- Huaxi Xu
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Affiliations: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
Published online on: April 21, 2017 https://doi.org/10.3892/mmr.2017.6500
Pages: 4291-4299

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Abstract

Glucocorticoid‑induced tumor necrosis factor receptor (GITR) is expressed at high levels on CD4+CD25+ regulatory T cells (Tregs). Following activation by its ligand (GITRL), GITR influences the activity of effector T cells and Tregs and participates in the development of numerous autoimmune and inflammatory diseases, including asthma. However, the GITR/GITRL expression level in lung tissue and its influence on group 2 innate lymphocytes (ILC2s) in asthma remains unclear. The present study detected the number of ILC2s and the expression levels of GITR and GITRL in the lung tissues of asthmatic mice by flow cytometry analysis, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction. The results demonstrated that the number of ILC2s and the expression levels of ILC2‑associated molecules (interleukin‑33 receptor ST2, RAR related orphan receptor A and inducible T cell costimulator) were increased in the lung tissues of asthmatic mice. The upregulated ILC2s were accompanied by an increased number of GITR‑positive cells in the spleen and lung tissues, and additionally an increased level of GITRL mRNA in lung tissue in asthma. In addition, increased mRNA expression levels of interleukin (IL)‑5 and IL‑13 were observed in the asthmatic lung, and there was a significant, positive correlation between the mRNA levels of GITR/GITRL and ILC2‑associated molecules. Therefore, GITRL treatment may increase the number of ILC2s and/or GITR‑positive cells in lung tissue. These results indicated that the activity of GITR‑expressing ILC2s may be enhanced via interaction of GITRL and GITR, which may contribute to pathogenesis of asthma. These findings present potential therapeutic targets for the treatment of asthma.

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